DESCRIPTION (Verbatim from the Applicant): This is a proposal to continue an investigation into the nonlinear stress-strain behavior of human cortical bone from the perspective of time-dependent damage accumulation processes. The damage accumulation processes that occur in normal human bone are not well understood. Characterizing these processes and developing predictive models have important implications for understanding skeletal fragility and bone remodeling. Achieving our long-term goal of predicting damage processes relevant to in vivo loading conditions depends on extending our work to understand how damage induced in one loading mode affects mechanical properties in other loading modes. The objective of the current proposal is to extend our initial experimental studies of time-dependent damage accumulation processes from single mode effects to multi-mode effects. The general hypotheses underlying our Specific Aims are: 1) damage induced by a given loading mode affects mechanical properties in all modes; 2) these interactions are dependent on the morphology of the micro-structural level damage. Specific Aims are: 1. Measure the effects of each single damage mode (tension, compression and torsion) in machined samples of human cortical bone on the mechanical property degradation across all loading modes. Specifically we will determine the effect of single-mode damage on viscoelastic properties and monotonic strength in tension, compression and torsion. 2. Measure the effects of combined damage mode (tension + torsion, compression + torsion) in machined samples of human cortical bone on the mechanical property degradation across all loading modes. Specifically we will determine the effects of combined-mode damage on viscoelastic properties and monotonic strength in tension, compression and torsion. 3. Obtain morphometric measures of the microstructural damage and correlate morphological features of micro-structural damage with measures of mechanical property degradation. Achieving these aims will yield information that is critical to development of models that can be used to predict damage accumulation under generalized loading conditions. The information identifying deleterious interactions between damage mode and mechanical degradation in multiple loading modes, and relating those interactions to damage morphology will also be of direct usefulness in knowledgeably addressing issues of skeletal fragility and alterations in damage behavior as a result of aging or disease.